Studies of the occurrence of mental illness in families have been useful in identifying familial forms of the illnesses but incompletely specify the nature and strength of genetic and environmental factors in etiology. We have previously reported that chronic schizophrenia and schizophrenia-like disorders occur at a significantly elevated rate in the biological relatives of chronic schizophrenia adoptees and not in their adoptive relatives. Our recent replication of this finding in a national register of nearly 15,000 Danish adoptees provides compelling evidence for the significant operation of genetic factors in the etiology of schizophrenia. Furthermore, our demonstration that the increased prevalence of schizophrenia in the biological families of adoptees does not differ significantly from that in the natural families of schizophrenic individuals indicates that the familial tendency in this disorder is an expression of genetic factors, and provides justification for the use of family studies to examine the modes of genetic transmission and to search for genetic linkages. We are currently using our material to derive empirically based criteria for the diagnosis of schizophrenia and related disordered in order to enhance the validity of these diagnosis and to determine the boundaries of the schizophrenia spectrum of disorders. Statistical methods developed during the course of our studies offer colleagues an approach to determining criteria for change when using multiple, potentially correlated, measures.